Treatment with Gold Nanoparticles Using Cudrania tricuspidata Root Extract Induced Downregulation of MMP-2/-9 and PLD1 and Inhibited the Invasiveness of Human U87 Glioblastoma Cells.

Sun Young Park,Geuntae Park,Beomjin Kim,Zhengwei Cui,Young-Whan Choi

doi:10.3390/ijms21041282

Sun Young Park, Geuntae Park + Show 3 more

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https://doi.org/10.3390/ijms21041282

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Abstract

In this study, we aimed to elucidate the anti-invasive effects of Cudrania tricuspidata root-gold nanoparticles (CTR-GNPs) using glioblastoma cells. We demonstrated the rapid synthesis of CTR-GNPs using UV-vis spectra. The surface morphology, crystallinity, reduction, capsulation, and stabilization of CTR-GNPs were analyzed using high resolution transmission electron microscopy (HR-TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). Furthermore, CTR-GNPs displayed excellent photocatalytic activity as shown by the photo-degradation of methylene blue and rhodamine B. Cell migration and invasion assays with human glioblastoma cells were performed to investigate the anti-invasive effect of CTR-GNPs on U87 cells that were treated with phorbol 12-myristate 13-acetate. The results show that CTR-GNPs can significantly inhibit both basal and phorbol 12-myristate 13-acetate (PMA)-induced migration and invasion ability. Importantly, treatment with CTR-GNPs significantly decreased the levels of metalloproteinase (MMP)-2/-9 and phospholipase D1 (PLD1) and protein but not PLD2, which is involved in the modulation of migration and the invasion of glioblastoma cells. These results present a novel mechanism showing that CTR-GNPs can attenuate the migration and invasion of glioblastoma cells induced by PMA through transcriptional and translational regulation of MMP-2/-9 and PLD1. Taken together, our results suggest that CTR-GNPs might be an excellent therapeutic alternative for wide range of glioblastomas.

Highlights

Glioblastoma is a devastating condition, and it is the leading cause of brain tumor-associated disability and mortality worldwide
We provide extensive evidence that the novel Cudrania tricuspidata root (CTR)-gold nanoparticles (GNPs) can attenuate the antiinvasive effects caused by both control and phorbol 12-myristate 13-acetate (PMA) stimulation by downregulating matrix metalloproteinases (MMPs)-2/MMP-9 and
We provide extensive evidence that the novel CTR-GNPs can attenuate the anti-invasive effects caused by both control and PMA stimulation by downregulating MMP-2/MMP-9 and phospholipase D1 (PLD1)

Summary

Introduction

Glioblastoma is a devastating condition, and it is the leading cause of brain tumor-associated disability and mortality worldwide. Malignant glioblastoma is characterized by high morbidity and mortality due to metastasis [1]. The survival rate of glioblastoma patients is still poor, mainly due to the resistance, reoccurrence, metastasis, and severe treatment side effects [2,3]. Multiple extraneural metastasis of glioblastoma is responsible for the high patient mortality and poses a major challenge in the treatment of glioblastoma due to its complexity and multistep process. Despite tremendous research efforts in recent times, effective, preventative, and disease-modifying treatment options against glioblastoma are not yet available [4,5,6]. The increased incidence of glioblastoma and the problems associated with the development of effective therapeutic alternatives against this disease have prompted researchers to explore nano-medical therapeutic strategies

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